tbuckley/cabot-search huggingface dataset:
Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection Among Children Aged 3–5 Years — Increasing Community Access to Testing Program, United States, July 2022–February 2023
Authors: Katherine E. Fleming-Dutra, Allison Avrich Ciesla, Lauren E. Roper, Zachary R. Smith, Joseph D. Miller, Emma K. Accorsi, Jennifer R. Verani, Nong Shang, Gordana Derado, Ryan E. Wiegand, Tamara Pilishvili, Amadea Britton, Ruth Link-Gelles
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Moderna COVID-19 vaccine primary series consists of two 25 μg doses separated by at least 4-8 weeks.† Pfizer-BioNTech COVID-19 vaccine primary series consists of three 3 μg doses, with at least 3-8 weeks between doses 1 and 2 and ≥8 weeks between doses 2 and 3. § At nearly all ICATT sites, test eligibility is restricted to persons aged ≥3 years.Therefore, this analysis was limited to children aged ≥3 years.¶ At test registration, caregivers reported the presence of any of the following COVID-19-like illness symptoms: fever, cough, shortness of breath, recent loss of sense of smell or taste, muscle pain, fatigue, chills, headache, sore throat, congestion or runny nose, vomiting, or diarrhea, which were reported to CDC as asymptomatic or symptomatic with one or more symptom.
Lysosomal lipid peroxidation regulates tumor immunity
Authors: Monika Bhardwaj, Jennifer J. Lee, Amanda M. Versace, Sandra L. Harper, Aaron R. Goldman, Mary Ann S. Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D. Winkler, Qin Liu, David W. Speicher, Ravi K. Amaravadi
Journal: Journal of Clinical Investigation (2023)

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport of NAC and rescue of LLP. PPT1 inhibition produced cell-intrinsic immunogenicity with surface expression of calreticulin that could only be reversed with NAC. DC661-treated cells primed naive T cells and enhanced T cell–mediated toxicity. Mice vaccinated with DC661-treated cells engendered adaptive immunity and tumor rejection in “immune hot” tumors but not in “immune cold” tumors. These findings demonstrate that LLP drives lysosomal cell death, a unique immunogenic form of cell death, pointing the way to rational combinations of immunotherapy and lysosomal inhibition that can be tested in clinical trials.
Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer
Authors: Chiara A. Cella, Maren Knoedler, Marcia Hall, Michele Arcopinto, Vincenzo Bagnardi, Lorenzo Gervaso, Stefania Pellicori, Francesca Spada, Maria G. Zampino, Paola S. Ravenda, Samuele Frassoni, Antonio Passaro, Monica Milano, Alice Laffi, Nicola Fazio, Florian Lordick
Journal: JAMA Network Open (2023)

Importance The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, Setting, and Participants ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main Outcomes and Measures The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 ( P &amp;amp;lt; .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and Relevance This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.
Errors in Affiliations
Authors: Yuanjie Mao, Wenjun Zhong
Journal: JAMA Oncology (2023)

Nancy U. Lin, MD; Rashmi K. Murthy, MD, MBE; Vandana Abramson, MD; Carey Anders, MD; Thomas Bachelot, MD, PhD; Philippe L. Bedard, MD; Virginia Borges, MMSc, MD; David Cameron, MD, MA; Lisa A. Carey, MD; A. Jo Chien, MD; Giuseppe Curigliano, MD, PhD; Michael P. DiGiovanna, MD, PhD; Karen Gelmon, MD; Gabriel Hortobagyi, MD; Sara A. Hurvitz, MD; Ian Krop, MD, PhD; Sherene Loi, MD, PhD; Sibylle Loibl, MD, PhD; Volkmar Mueller, MD; Mafalda Oliveira, MD, PhD; Elisavet Paplomata, MD; Mark Pegram, MD; Dennis Slamon, MD; Amelia Zelnak, MD, MSc; Jorge Ramos, DO; Wentao Feng, PhD; Eric Winer, MD
Ara h 1 but not Ara h 2 strongly adheres to oral epithelium and remains in the oral area upon peanut release
Authors: Rafael Valdelvira, Guadalupe Garcia‐Medina, Celine Galleani, Vera Kralova, Jesus F. Crespo, Beatriz Cabanillas
Journal: Allergy (2023)

Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Worsening Rash in a Patient With Metastatic Breast Cancer
Authors: Michael J. Pierro, April J. Zhang, Lubna N. Chaudhary
Journal: JAMA Oncology (2023)

A 56-year-old woman with metastatic hormone receptor–positive, ERBB2-negative breast cancer presents with pruritic, erythematous, scaly macules and papules on her forearms, faces, chest, and upper back. What is your diagnosis?
States’ Methods for Capturing and Reporting Local Responses to Suspected Nonfatal Drug Overdoses
Authors: Christian Johnson, Megan Catlin, Lisa Sinow, Rahul Gupta, David R. Holtgrave
Journal: JAMA (2023)

This study examines the available data used to surveil state-level drug overdoses and characterizes them based on their timeliness, drug involvement, and specification of nonfatal outcomes.
Using fecal immmunochemical cartridges for gut microbiome analysis within a colorectal cancer screening program
Authors: Stefanie Brezina, Martin Borkovec, Andreas Baierl, Fabienne Bastian, Andreas Futschik, Nikolaus Gasche, Thomas Gruenberger, Michael Hallas, Christian Jannsen, Gernot Leeb, Rebecca Lutz, Barbara Sladek, Andrea Gsur
Journal: Gut Microbes (2023)

The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays a role in the etiology of CRC, microbiome-based biomarkers in combination with FIT could be a promising tool for optimizing CRC screening. Therefore, we evaluated the usability of FIT cartridges for microbiome analysis and compared it to Stool Collection and Preservation Tubes. Corresponding FIT cartridges as well as Stool Collection and Preservation Tubes were collected from participants of the B-PREDICT screening program to perform 16S rRNA gene sequencing. We calculated intraclass correlation coefficients (ICCs) based on center log ratio transformed abundances and used ALDEx2 to test for significantly differential abundant taxa between the two sample types. Additionally, FIT and Stool Collection and Preservation Tube triplicate samples were obtained from volunteers to estimate variance components of microbial abundances. FIT and Preservation Tube samples produce highly similar microbiome profiles which cluster according to subject. Significant differences between the two sample types can be found for abundances of some bacterial taxa (e.g. 33 genera) but are minor compared to the differences between the subjects. Analysis of triplicate samples revealed slightly worse repeatability of results for FIT than for Preservation Tube samples. Our findings indicate that FIT cartridges are appropriate for gut microbiome analysis nested within CRC screening programs.
Noninvasive Detection of Smooth Muscle Cell-Derived Hot Spots to Study Atherosclerosis by PET/MRI in Mice
Authors: Susanne Feil, Dimitri Stowbur, Barbara F. Schörg, Walter Ehrlichmann, Gerald Reischl, Manfred Kneilling, Bernd J. Pichler, Robert Feil
Journal: Circulation Research (2023)
Optimal dose of adrenaline auto‐injector for children and young people at risk of anaphylaxis: A phase <scp>IV</scp> randomized controlled crossover study
Authors: Nandinee Patel, Emily Isaacs, Bettina Duca, Nanthagopan Nagaratnam, Jackie Donovan, Sara Fontanella, Paul J. Turner
Journal: Allergy (2023)

Guidelines recommend intramuscular injection of 500 μg adrenaline (epinephrine) for anaphylaxis in teenagers and adults; however, most autoinjectors deliver a maximum 300 μg dose. We evaluated plasma adrenaline levels and cardiovascular parameters (including cardiac output) following self-injection with 300 μg or 500 μg adrenaline in teenagers at risk of anaphylaxis.
Putative Signals of Generalist Plant Species Adaptation to Local Pollinator Communities and Abiotic Factors
Authors: Léa Frachon, Luca Arrigo, Quint Rusman, Lucy Poveda, Weihong Qi, Giovanni Scopece, Florian P Schiestl
Journal: Molecular Biology and Evolution (2023)

Abstract The reproductive success of flowering plants with generalized pollination systems is influenced by interactions with a diverse pollinator community and abiotic factors. However, knowledge about the adaptative potential of plants to complex ecological networks and the underlying genetic mechanisms is still limited. Based on a pool-sequencing approach of 21 natural populations of Brassica incana in Southern Italy, we combined a genome-environmental association analysis with a genome scan for signals of population genomic differentiation to discover genetic variants associated with the ecological variation. We identified genomic regions putatively involved in the adaptation of B. incana to the identity of local pollinator functional categories and pollinator community composition. Interestingly, we observed several shared candidate genes associated with long-tongue bees, soil texture, and temperature variation. We established a genomic map of potential generalist flowering plant local adaptation to complex biotic interactions, and the importance of considering multiple environmental factors to describe the adaptive landscape of plant populations.
Coordinated activation of c-Src and FOXM1 drives tumor cell proliferation and breast cancer progression
Authors: Ipshita Nandi, Harvey W. Smith, Virginie Sanguin-Gendreau, Linjia Ji, Alain Pacis, Vasilios Papavasiliou, Dongmei Zuo, Stella Nam, Sherif S. Attalla, Sung Hoon Kim, Sierra Lusson, Hellen Kuasne, Anne-Marie Fortier, Paul Savage, Constanza Martinez Ramirez, Morag Park, John A. Katzenellenbogen, Benita S. Katzenellenbogen, William J. Muller
Journal: Journal of Clinical Investigation (2023)

Activation of the tyrosine kinase c-Src promotes breast cancer progression and poor outcomes, yet the underlying mechanisms are incompletely understood. Here, we have shown that deletion of c-Src in a genetically engineered model mimicking the luminal B molecular subtype of breast cancer abrogated the activity of forkhead box M1 (FOXM1), a master transcriptional regulator of the cell cycle. We determined that c-Src phosphorylated FOXM1 on 2 tyrosine residues to stimulate its nuclear localization and target gene expression. These included key regulators of G2/M cell-cycle progression as well as c-Src itself, forming a positive feedback loop that drove proliferation in genetically engineered and patient-derived models of luminal B-like breast cancer. Using genetic approaches and small molecules that destabilize the FOXM1 protein, we found that targeting this mechanism induced G2/M cell-cycle arrest and apoptosis, blocked tumor progression, and impaired metastasis. We identified a positive correlation between FOXM1 and c-Src expression in human breast cancer and show that the expression of FOXM1 target genes predicts poor outcomes and associates with the luminal B subtype, which responds poorly to currently approved therapies. These findings revealed a regulatory network centered on c-Src and FOXM1 that is a targetable vulnerability in aggressive luminal breast cancers.
Bidirectional Associations Between Adiposity and Cognitive Function and Mediation by Brain Morphology in the ABCD Study
Authors: Mohammad Nazmus Sakib, John R. Best, Peter A. Hall
Journal: JAMA Network Open (2023)

Most epidemiologic studies examine the brain as an outcome in relation to adiposity (ie, the brain-as-outcome perspective), but it is also a potential risk factor associated with adiposity accumulation over time (ie, the brain-as-risk factor perspective). The bidirectionality hypothesis has not been fully explored in adolescent samples previously.To assess bidirectional associations between adiposity and cognitive function in youth and test mediational pathways through brain morphology (specifically the lateral prefrontal cortex [LPFC]), lifestyle behaviors, and blood pressure.This cohort study uses data (wave 1-3; 2 years of follow-up) from the Adolescent Brain Cognitive Development (ABCD) Study, a long-term longitudinal investigation of brain development in the United States launched in 2015, which recruited 11 878 children aged 9 to 10 years at inception. Data analysis was performed from August 2021 to June 2022.Multivariate multivariable regression analyses were used to assess bidirectional associations of indicators of cognitive function (eg, executive function, processing speed, episodic memory, receptive vocabulary and reading skills) and adiposity (eg, body mass index z scores [zBMI] and waist circumference [WC]). Mediators considered for this investigation were lifestyle variables (eg, diet and physical activity), blood pressure, and the morphology of the LPFC and its subregions.A total of 11 103 individuals (mean [SD] age, 9.91 [0.6] years; 5307 females [48%]; 8293 White individuals [75%] and 2264 Hispanic individuals [21%]) were included in the current study. Multivariate multivariable regression analyses revealed that higher baseline zBMI and WC were associated with worse follow-up episodic memory (β, -0.04; 95% CI, -0.07 to -0.01) and better vocabulary (β, 0.03; 95% CI, 0.002 to 0.06) task performance, in covariate adjusted models. Similarly, superior baseline executive function (zBMI: β, -0.03; 95% CI, -0.06 to -0.01; WC: β, -0.04; 95% CI, -0.07 to -0.01) and episodic memory (zBMI: β, -0.04; 95% CI, -0.07 to -0.02; WC: β, -0.03; 95% CI, -0.06 to -0.002) task performance were associated with better follow-up adiposity status in covariate adjusted models. Cross-lagged panel models with latent variable modeling had a bidirectional association with executive function task performance (brain-as-outcome: β, -0.02; 95% CI, -0.05 to -0.001; brain-as-risk factor: β, -0.01; 95% CI, -0.02 to -0.003). The hypothesized associations were statistically mediated by LPFC volume and thickness, physical activity, and blood pressure.In this cohort study, executive function and episodic memory were bidirectionally associated with adiposity indices over time in this adolescent sample. These findings suggest that the brain can be both a risk factor and an outcome of adiposity; this complex bidirectional association should be taken into account in future research and clinical practice.
Correction: SELP Asp603Asn and severe thrombosis in COVID-19 males
Authors: Chiara Fallerini, Sergio Daga, Elisa Benetti, Nicola Picchiotti, Kristina Zguro, Francesca Catapano, Virginia Baroni, Simone Lanini, Alessandro Bucalossi, Giuseppe Marotta, Francesca Colombo, Margherita Baldassarri, Francesca Fava, Giada Beligni, Laura Di Sarno, Diana Alaverdian, Maria Palmieri, Susanna Croci, Andrea M. Isidori, Simone Furini, Elisa Frullanti, Alessandra Renieri, Francesca Mari
Journal: Journal of Hematology & Oncology (2023)
Sinoatrial Node Radiation Dose and Atrial Fibrillation in Patients With Lung Cancer—Reply
Authors: Kyung Hwan Kim, Jaewon Oh, Hong In Yoon
Journal: JAMA Oncology (2023)

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Letter to the editor: Highly pathogenic influenza A(H5N1) viruses in farmed mink outbreak contain a disrupted second sialic acid binding site in neuraminidase, similar to human influenza A viruses
Authors: Erik de Vries, Cornelis AM de Haan
Journal: Eurosurveillance (2023)

Preview this article: Letter to the editor: Highly pathogenic influenza A(H5N1) viruses in farmed mink outbreak contain a disrupted second sialic acid binding site in neuraminidase, similar to human influenza A viruses, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/28/7/eurosurv-28-7-5-1.gif
Paroxysmal nocturnal hemoglobinuria: Where are we going
Authors: Austin G. Kulasekararaj, Ioanna Lazana
Journal: American Journal of Hematology (2023)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare nonmalignant clonal hematological disorder that is characterized by a deficiency of the GPI-linked complement regulators on the membrane of hematopoietic cells, which renders them susceptible to complement-mediated damage. Intravascular hemolysis (IVH), increased tendency for thrombosis, and bone marrow failure constitutes hallmark features of the disease and are associated with high morbidity and mortality. The introduction of C5 inhibitors radically changed disease outcomes, offering a near-normal life expectancy to PNH patients. However, residual IVH and extravascular hemolysis (EVH) continue to occur during C5-inhibitor treatment, leaving a significant proportion of patients' anemic and some remaining transfusion dependent. Quality of life (QoL) has also been an issue with the regular intravenous (IV) administrations of the currently licensed C5 inhibitors. This has led to the exploration and development of novel agents, targeting different parts of the complement cascade, or having different formulations allowing for self-administration. Longer-acting and subcutaneous formulations of C5 inhibitors have shown equal safety and efficacy, whereas the development of proximal complement inhibitors is changing completely the therapeutic landscape of PNH, limiting both IVH and EVH and showing superior efficacy over C5 inhibitors, especially in improving haemoglobin. Combination treatments have also been tested with promising results. This review summarizes the current therapeutic options, gaps in anti-complement therapy and discusses emerging therapeutic approaches for PNH.
Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance
Authors: Mathias K.-M. Herzog, Monica Cazzaniga, Audrey Peters, Nizar Shayya, Luca Beldi, Siegfried Hapfelmeier, Markus M. Heimesaat, Stefan Bereswill, Gad Frankel, Cormac G.M. Gahan, Wolf-Dietrich Hardt
Journal: Gut Microbes (2023)

Globally, enteropathogenic bacteria are a major cause of morbidity and mortality.1-3Campylobacter, Salmonella, Shiga-toxin-producing Escherichia coli, and Listeria are among the top five most commonly reported zoonotic pathogens in the European Union.4 However, not all individuals naturally exposed to enteropathogens go on to develop disease. This protection is attributable to colonization resistance (CR) conferred by the gut microbiota, as well as an array of physical, chemical, and immunological barriers that limit infection. Despite their importance for human health, a detailed understanding of gastrointestinal barriers to infection is lacking, and further research is required to investigate the mechanisms that underpin inter-individual differences in resistance to gastrointestinal infection. Here, we discuss the current mouse models available to study infections by non-typhoidal Salmonella strains, Citrobacter rodentium (as a model for enteropathogenic and enterohemorrhagic E. coli), Listeria monocytogenes, and Campylobacter jejuni. Clostridioides difficile is included as another important cause of enteric disease in which resistance is dependent upon CR. We outline which parameters of human infection are recapitulated in these mouse models, including the impact of CR, disease pathology, disease progression, and mucosal immune response. This will showcase common virulence strategies, highlight mechanistic differences, and help researchers from microbiology, infectiology, microbiome research, and mucosal immunology to select the optimal mouse model.